Highly organized and biologically functional engineered tissues are desirable in repairing or replacing diseased tissues. Much effort has been focused on developing biodegradable polymer scaffolds suitable for tissue engineering. An ideal scaffold should mimic the structural and purposeful profile of materials found in the natural extracellular matrix (ECM) architecture. Biocompatible and biodegradeable polymers are common materials for scaffold fabrication. Nanofibers of biocompatible polymers prepared by electrospinning are considered a favorable material for tissue engineering scaffolds due to their high surface area to volume ratio desirable for enhanced cell attachment. Biocompatible polymers include poly(L-lactic-co-epsilon-caprolactone) (P(LLA-CL)) and poly(D,L-lactide-co-glycolide) (PLGA) (See Lee et al., Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast, Biomaterials, 26: 1261 (2004) and Xu et al., Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering, Biomaterials 25:877 (2004)).
In addition to the physical and/or chemical properties of the scaffold materials, mechanical forces may also play an important role in cell growth and tissue formation. Several investigators have reported that cyclic mechanical stretch increases ECM production in cultured fibroblasts on flexible membranes (See e.g., E. C. Breen, Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro. J Appl Physiol 88: 203 (2000)). It has also been reported that mechanical strain may stimulate the release of a growth factor (See e.g., Sudhir et al., Mechanical strain stimulates a mitogenic response in coronary vascular smooth muscle cells via release of basic fibroblast growth factor. Am J Hypertens. 14:1128 (2001)). Moreover, mechanical strain may affect the orientation of the cytoskeleton, which, in turn, determines the orientation, alignment and mobility of a cell (See Ingber, Cellular tensegrity: exploring how mechanical changes in the cytoskeleton regulate cell growth, migration, and tissue pattern during morphogenesis. Int Rev Cytol 150:173 (1994)). Therefore, mechanical strain is instrumental in the formation of many types of tissues, such as connective and muscle tissues.
Fluid flow is another important factor in tissue engineering. Cells require nutrients and oxygen to grow, and waste materials and dead cells must be promptly removed to avoid deleterious effects on healthy cells. In tissue engineering, however, these tasks are typically accomplished through diffusion alone. While diffusion may provide sufficient fluid flow for thin tissues, it is usually insufficient for scaffolds thicker than 200 μm. In order to solve this problem, Stankus et al. employed a perfusion bioreactor to increase fluid flow in the culture (Stankus et al., Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix, Biomaterials 27:735 (2006)). However, the bioreactor requires connection to the cell growing chamber and is invasive on the host. There is therefore a need for a minimally invasive method that can both stimulate the cells and promote fluid flow.
Another front of biomedical engineering has been focused on developing devices for efficient and accurate delivery of drugs. One of the goals of this effort has been to create a vehicle that is able to deliver and release compounds at a diseased site in the body. Liposome-based design has been the focus of one line of research; however, it has many shortcomings. More recently, sol-gel technique has been widely used to fabricate porous nanoparticles within a polymer for controlled release of drugs (See generally, Asif et al., Fabrication of nanoparticles within polymeric pores for controlled release of drug. Pak J Pharm Sci., 19:73 (2006)). None of the currently available methods afford the capability to remotely control the release of drugs through a non-invasive mechanism.
Hence, there is a need for a device and a mechanism for delivery of drugs or other materials to target site in vivo where the release of the materials may be controlled remotely by the operation of a magnetic field so as to overcome one or more of the issues and problems identified above.